Previous attempts to produce immunity in syphilis in experimental animals did not provide satisfactory results. The most direct method to determine the mechanism of immunity would be to confer it on normal recipients by transferring antibodies or lymphoid cells from immune animals. Such experimental approach requires inbred animals. Rabbit is the most susceptible laboratory animal for experimental syphilis, but it is far from being the ideal model. Inbred rabbit is not readily available and the responses to T. pallidum infection involve a great deal of non-specificity. Guinea pig, although comparatively less susceptible to infection, responds more restrictively (possible more specific) producing only treponemal IgG antibodies (no IgG or cardiolipin antibodies) and the T cells respond to T. pallidum antigen but not to T. phagedenis Reiter. Guinea pig may provide information not extractable from rabbit. We are proposing to use inbred strain 2 guinea pigs to examine: a) The susceptibility to infection with various wild strains of T. pallidum. If no differences are found the presently established Nichols strain to which they are susceptible up to 100% when used in appropriate concentration will be used for all experiments. b) The time at which the immune resistance is established, and to determine by transfer experiments whether it is controlled by humoral or cellular mechanisms. c) The specificity of the treponemal antibodies produced in guinea pig and compare it with those produced in rabbits. The guinea pig model, in addition to the information on the mechanisms of immunity, may also provide a tool for evaluation of treponemal antigens produced by DNA hybridization or potential vaccines for syphilis; the necessary background information for future studies of the genetic factors controlling immunity and for studying natural resistance to T. pallidum.